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B W Zweifach

Publications and source records attributed to B W Zweifach.

At least 37 records · Page 2Linked to original sources
PubMed1995

Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids.

Leukocyte adhesion is a key factor in the pathogenesis of organ injury following a variety of stimuli. In this study we have addressed the role of leukocyte adhesion in hypertensives as a risk factor for organ injury. In the spontaneously hypertensive rat (SHR), the number of circulating leukocytes and their level of activation are significantly increased compared with its normotensive control, the Wistar-Kyoto rat (WKY). We have demonstrated that elevated levels of glucocorticoid in SHR suppress P-selectin-mediated leukocyte-endothelial interaction in the microcirculation. It is possible that the disturbance in leukocyte-endothelial interactions may result in an elevated number of leukocytes in the circulation. The aim of the present study was to investigate the contribution of the adrenal glands to the disturbance in leukocyte behavior in SHR by subjecting the animals to bilateral adrenalectomy and investigating the effect of hydrocortisone. In addition, we have studied by immunohistochemistry the expression of the endothelial adhesion molecule, P-selectin, in response to histamine in the mesenteric venules of normal and adrenalectomized SHR and WKY. The elevated blood pressure, above-normal leukocyte counts, and elevated number of activated neutrophils (nitroblue tetrazolium test) in SHR were blunted after adrenalectomy. The blunted histamine-induced leukocyte-endothelial interaction in the mesenteric venules of SHR was restored after adrenalectomy. Treatment with hydrocortisone significantly attenuated the elevated leukocyte adhesion in the adrenalectomized SHR as well as in WKY. The suppressed P-selectin expression in SHR mesentery was restored after adrenalectomy. In conclusion, the subnormal leukocyte-endothelial interaction in response to an inflammatory stimulation in SHR is abolished after adrenalectomy, suggesting a relationship between the altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensives.

Adrenal Cortex Hormones↗
PubMed1994

Impaired leukocyte-endothelial cell interaction in spontaneously hypertensive rats.

Hypertension is associated with a progressive organ injury whose etiology remains largely speculative. An increasing database shows that activated leukocytes, while affording an important immune protection, may be a contributing factor to several of the pathogenetic features of the hypertension syndrome. The purpose of this study was to determine the extent to which the glucocorticoid pathway may be involved in the atypical kinetics of leukocytes in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. The typical venular leukocyte adhesion induced by histamine application was significantly lower in SHR, and a comparison of normalized leukocyte rolling velocity (VWBC/VRBC) showed the values to be significantly higher in SHR relative to WKY controls. This abnormal trend in adherent leukocyte numbers and in VWBC/VRBC values could be counteracted when SHR were pretreated with RU 486, a synthetic glucocorticoid inhibitor, and restored to the levels observed in WKY rats. Anti-P-selectin monoclonal antibody (PB1.3) attenuated in SHR and WKY rats the increment of adherent leukocyte numbers as well as the decrement of VWBC/VRBC value that developed under combined histamine and RU 486 superfusion. Furthermore, an anti-intercellular adhesion molecule-1 monoclonal antibody (1A29) served to attenuate the increment of adherent leukocyte number induced by a combination of histamine and RU 486 superfusion in WKY rats and SHR. The results indicate that the deficient leukocyte-endothelial cell interaction in SHR can be circumvented by a glucocorticoid inhibitor.

Animals↗
PubMed1994

Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation.

BACKGROUND: Although leukocyte adhesion and capillary plugging are postulated to play a role in postischemic tissue injury, there is only limited evidence demonstrating the relationship between tissue leukocyte accumulation and cell injury in terms of their temporal sequence and spatial distribution. EXPERIMENTAL DESIGN: This study was designed to study in vivo neutrophil behavior and its correlation with cell injury in postischemic skeletal muscle microcirculation. The microcirculation of the rat spinotrapezius muscle was observed in vivo using dual-color digital microfluorography to simultaneously visualize leukocyte traffic and cell death (irreversible nuclear damage) on the basis of carboxyfluorescein diacetate succinimidyl ester and propidium iodide, respectively. A 1-hour period of hemorrhagic hypotension (40 mm Hg) followed by reperfusion was carried out to induce muscle injury. RESULTS: Hypotension was followed by an increase in leukocyte recruitment in two different ways: capillary obstruction and venular adhesion. Upon reperfusion, a majority of the leukocytes were initially dispersed from the muscle capillaries and venules, but then the number of leukocytes plugging capillaries and adherent to venules increased again in a time-dependent manner. The number of leukocytes obstructing capillaries was closely correlated with the postischemic systemic blood pressure. The cell injury became detectable initially at the end of the hypotensive period and then increased explosively after reperfusion before a significant leukocyte accumulation. Reperfusion-induced early nuclear injury was seen predominantly in reperfused capillaries without plugging leukocytes. A majority of the initially damaged nuclei were those of myocytes in the pericapillary space, but no nuclei of capillary endothelium was involved. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate, a novel inhibitor of xanthine oxidase, significantly attenuated the early increase in muscle injury and subsequent venular leukocyte adhesion after reperfusion. CONCLUSIONS: These results suggest the involvement of an endothelium-dependent mechanism involving xanthine oxidase in postischemic irreversible myocyte injury. It is conceivable that leukocytes adherent to venules as well as those plugging capillaries play only minor roles in the initial mechanism of reperfusion injury.

Animals↗
PubMed1993

In vivo visualization of oxidative changes in microvessels during neutrophil activation.

This study was designed to characterize temporal changes of oxidative metabolism in microvascular endothelium in vivo associated with neutrophil adhesion and diapedesis. The rat mesentery was loaded with dichlorofluorescein (DCFH) diacetate, a hydroperoxide-sensitive fluorescent probe that is trapped within viable cells as a nonfluorescent form and is converted to fluorescent dichlorofluorescein (DCF) by hydroperoxides. The fluorescent light emission was recorded with digital microscopy and its camera response was calibrated by superfusion of the mesentery with known concentrations of hydroperoxides. After rinsing with a precursor-free solution, it was possible to observe both the neutrophil adhesion and fluorescence changes in venular endothelium during superfusion with platelet-activating factor (PAF, 100 nM) by alternately changing light sources. In the PAF-treated animals, DCF fluorescence in the venular wall was markedly elevated concurrent with an increase in the number of adherent neutrophils. An onset of a significant DCF fluorescence was observed as early as 10 min after PAF application. The venular oxidative changes were co-localized with neutrophils adhering to the endothelium or migrating into the interstitium. The oxidative impact in the venular wall superfused with 100 nM PAF for 40 min was equivalent to that induced by the 10-min superfusion of 0.8 mM of tert-butyl hydroperoxide. Pretreatment with dipyridyl, an iron chelator, or dimethylthiourea, a hydroxyl radical scavenger, significantly attenuated the PAF-induced oxidative changes in the venule but had little effect on neutrophil adhesion. These findings suggest that an endothelial cell-dependent mechanism involving an iron-catalyzed reaction may have a role in enhancement of neutrophil-mediated oxidative stress in venular endothelium.

2,2'-Dipyridyl↗
PubMed1991

Penetration of the systemic blood pressure into the microvasculature of rat skeletal muscle.

A series of arterial micropressure measurements in different skeletal muscles of the Wistar-Kyoto and spontaneously hypertensive rat is presented. The micropunctures were carried out with minimal surgical intervention through small skin incisions and the micropressures were recorded simultaneously with femoral artery pressures. The measurement sites were located at the entry points into the muscles for the proximal and distal supply arteries and at the midpoint of the arteriolar arcade bridge which directly connects these two supply arteries in the center of the muscle parenchyma. In contrast to feed artery pressure values from exteriorized muscles, which in the past have been reported to be as low as 40 mm Hg, the current mean pressure values are substantially higher and in the range between 70 and 100 mm Hg, equivalent to 70 to 90% of the mean systemic pressure. Systolic and diastolic values exhibit comparable trends to the mean pressures and they are similar in muscles at different locations in the body. Although in spontaneously hypertensive rats the absolute pressures were significantly higher compared with their controls, the normalized pressures were virtually identical at the locations used in this study. These data indicate that the absolute pressure in the central arteries of spontaneously hypertensive animals is reduced to a greater degree than in Wistar-Kyoto rats, while in both strains the major pressure reduction in skeletal muscle still occurs in the microcirculation.

Animals↗
PubMed1991

Leukocyte counts and activation in spontaneously hypertensive and normotensive rats.

The etiology for the progressive organ injury in hypertension is largely speculative. Recent studies have shown that leukocytes play a key role in several cardiovascular diseases. As an initial step toward investigating the role of leukocytes in hypertension, we measured leukocyte counts and spontaneous activation of granulocytes of freshly drawn unseparated blood samples in spontaneously hypertensive rats and in their normotensive counterpart, Wistar-Kyoto rats. The animals were derived from one breeder in the United States and from two breeders in Europe. Total leukocyte counts in young, mature, and old hypertensive rats were 50-100% above the controls. The number of granulocytes in mature and old spontaneously hypertensive rats in more than 100% elevated compared with control rats. In young hypertensive rats the mean granulocyte count was only slightly elevated. The number of spontaneously activated granulocytes, as detected by the nitroblue tetrazolium reduction, increases with age in both species; in mature spontaneously hypertensive rats, it is more than 300% above the values in the controls. Furthermore, in mature hypertensive rats the number of monocytes, activated monocytes, and the lymphocyte count are also significantly elevated over the values in the normotensive controls. It is proposed that these elevated leukocyte counts may constitute an enhanced risk for organ injury in the spontaneously hypertensive rat.

Animals↗
PubMed1991

Polymorphonuclear neutrophil contribution to induced tolerance to bacterial lipopolysaccharide.

The objective of this study was to investigate mechanisms by which polymorphonuclear neutrophils (PMNs) contribute to the tolerance induced by repeated lipopolysaccharide (LPS) injections. Tolerance was developed by daily intraperitoneal injections of sublethal doses of LPS for 4 days (LPS-tolerant group); controls were not pretreated (LPS-control group). Both groups were challenged with 9 mg/kg i.v. Escherichia coli LPS, a dose that resulted in 25% survival in LPS-control rats compared with 100% survival in LPS-tolerant rats. LPS injection caused an initial neutropenia in both groups. The neutropenia persisted throughout the experiment in LPS-control rats, whereas in LPS-tolerant rats the circulating PMN count increased dramatically; after 6 hours, the PMN count was 16-fold higher than that in LPS-control rats. Activation of circulating PMNs, PMN adhesion to nylon fibers, and tumor necrosis factor/cachectin activity were all increased in control rats given LPS. In contrast, LPS-tolerant rats had low activation of circulating PMNs, no trend for PMN adhesion to nylon fibers, and markedly reduced tumor necrosis factor activity. To determine whether neutropenia was associated with a trapping of PMNs in the microcirculation, we used a carbon perfusion technique 6 hours after LPS injection and examined histological sections of the myocardium. All of the arterioles and venules in both groups contained carbon; only capillaries showed evidence of obstruction. A significantly higher percentage of obstructed capillaries was observed in LPS-control rats than in LPS-tolerant rats. Obstruction of capillaries was consistently associated with trapped leukocytes. We conclude that PMN cytotoxicity induced by LPS involves microcirculatory entrapment and activation of PMNs. Repeated LPS pretreatment reduces dramatically circulating PMN activation and adhesion and is associated with an elevated circulating PMN count, a low degree of microvascular plugging, and survival after a normally lethal dose of LPS.

Animals↗
PubMed1990

Wall structure of arteries and arterioles feeding the spinotrapezius muscle of normotensive and spontaneously hypertensive rats.

Vessel wall structure in feed arteries and their hierarchical ramifications were investigated in a rat skeletal muscle. Emphasis was placed on the transition of wall structure elements from the axillary and thoracodorsal arteries to the feeder arteries and the arcade and transverse arterioles forming the microcirculation of the spinotrapezius muscle. Semi-thin sections, prepared for light microscopy, and ultra-thin sections for electron microscopy were used to compare mature (15-20 week old) normotensive and hypertensive animals. The results demonstrate a gradual transition of the elastica intima and the smooth muscle from the central arteries towards the arterioles, accompanied by an attenuation of the adventitia. The elastica intima in 60-40 microns arcade arterioles is reduced from a continuous sheet in the central arteries to single fibers oriented parallel to the vessel axis. The multiple layers of smooth muscle cells at the level of the feeder arteries are reduced in the majority of arcade arterioles and in transverse arterioles to a single smooth muscle coat. Comparisons of the smooth muscle mass per unit length of vessel at selected sites of normotensive and spontaneously hypertensive rats show evidence for some degree of wall hypertrophy in the axillary artery, but no evidence for wall hypertrophy in arterioles of the microcirculation. There is no evidence of a pressure-mediated structural medial wall hypertrophy along this peripheral vascular pathway.

Animals↗
PubMed1988

Granulocytes and no-reflow phenomenon in irreversible hemorrhagic shock.

Recent evidence shows that circulating granulocytes play an important role in capillary stasis and tissue injury. We investigated two aspects of the problem in a Wiggers hemorrhagic shock model of the rat: the survival rate and the microvascular no-reflow phenomenon. A conventional group of rats with normal blood cells and a neutropenic group of rats pretreated with intraperitoneal antigranulocyte antibody were used to evaluate the effects of granulocytes. Two hemorrhagic shock protocols (HSP) were carried out. In HSP-1, the rats were subjected to 40 mm Hg mean arterial pressure for 3 hours. The conventional group (n = 11) showed a 36% survival rate compared with 100% in the neutropenic group (n = 6). In HSP-2, the hypotension was more severe, 30 mm Hg mean arterial pressure for 7 hours. There were no survivors in the conventional group (n = 8), compared with a 100% survival rate in the neutropenic group (n = 6). The extent, location, and mechanism of the no-reflow phenomenon was investigated by examining histological sections from several organs after infusion of a contrast medium to mark vessels with flow in a control group without shock and in the HSP-2 model 2 hours after blood replacement. The arterioles and venules uniformly contained contrast medium in all three groups; only capillaries showed no-reflow. A significantly higher percentage of no-reflow was observed in the capillaries of the conventional shock group than in the neutropenic shock group. We concluded that the obstruction of capillaries was largely due to trapped granulocytes, suggesting that these leukocytes play a key role in the capillary no-reflow phenomenon and survival from hemorrhagic shock.

Animals↗
PubMed1987

Microvascular tone in a skeletal muscle of spontaneously hypertensive rats.

We studied the degree of arteriolar smooth muscle constriction in the spinotrapezius muscle microcirculation of spontaneously hypertensive rats and their normotensive controls, Wistar-Kyoto rats. The constriction was expressed in the form of a nondimensional tone as the difference between steady state and dilated diameter (after papaverine treatment) divided by the dilated diameter. Both animal strains showed on average a progressive increase of tone toward the more distal arterioles, with a peak tone being reached in the transverse arterioles. Tone values in the hypertensive animals were consistently elevated. The number of arterioles that had more than 5% tone (so-called responder arterioles) was higher in the hypertensive animals. These studies suggest that, besides the anatomical adjustments documented earlier in our laboratory in the arteriolar network of this muscle, functional adjustments in the form of an elevated microvascular tone are associated with the elevated resistance in spontaneously hypertensive rats.

Animals↗
PubMed1987

Analysis of microvascular network in bulbar conjunctiva by image processing.

A digital image processing procedure has been developed for obtaining quantitative morphometric data on the microcirculatory network in the human bulbar conjunctiva. Highlights of this semi-automated approach include: 1. extraction of morphometric information that cannot be readily obtained by manual methods--length, diameter, and diffusion distributions; 2. speed and consistency in data generation--only 10 minutes are required to scan and to analyze 6.7 mm2 of conjunctiva microvasculature. The variation was less than 5% when images of the same area in the same eye were subjected to analysis at different times; 3. avoid the human bias factor--the data obtained by repeated analysis of the same negative varied by less than 0.02%.

Conjunctiva↗
PubMed1986

The microvasculature in skeletal muscle. II. Arteriolar network anatomy in normotensive and spontaneously hypertensive rats.

A quantitative comparison of the anatomical arrangement of arterioles in the skeletal muscle of mature (16 to 20-week-old) Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) is provided. In both species several feeding arterioles supply blood to a network of arterioles covering the entire muscle, designated as arcade arterioles. The connections from the arcade arterioles to the capillary network are provided by the transverse arterioles. Comparison of the spinotrapezius muscle of the WKY and the SHR shows several types of rearrangement of the network. In both species there is a wide distribution of vessel size in the arcade and transverse arterioles. The length of the arcade arterioles per unit muscle volume is higher in the SHR, forming a denser network. There are almost twice as many transverse arteriolar trees per unit tissue volume in hypertensive animals although on the average each transverse tree has shorter branches. No evidence for significant anatomical rarefaction was found among arcade and transverse arterioles. Arcade arterioles following maximal dilation were found to be 25% narrower in the SHR, whereas for transverse arterioles no differences in diameter could be detected under these vasodilated conditions.

Animals↗
PubMed1986

Network anatomy of arteries feeding the spinotrapezius muscle in normotensive and hypertensive rats.

An understanding of blood flow requires a detailed picture of vascular and microvascular anatomy. To this end an investigation of the arteries feeding the spinotrapezius muscle in normotensive and spontaneously hypertensive rats was performed. Arteries were dilated and filled with resin materials and analyzed quantitatively for their network pattern and vessel geometry. The results show that there exists extensive meshworks of interconnected arteries forming an interogan plexus. The spinotrapezius muscle has multiple inflows from the thoracodorsal and intercostal arteries which interconnect in an arcade network in the muscle. Some but not all arteries of hypertensive rats are narrower in the dilated state at 100 mm Hg inflation pressure than their controls. Arterioles within the muscle proper, however, are not significantly different, suggesting that lumen narrowing of structural origin is progressively reduced towards the microcirculation.

Animals↗
PubMed1985

Microvascular adjustments during irreversible hemorrhagic shock in rat skeletal muscle.

A study was made of microvessel response to hemorrhagic hypotension and the subsequent restoration of blood volume. The experiments were conducted on anesthetized rats in which the cremaster muscle was exteriorized for intravital microscopy. Variables measured during hypotension (40 mm Hg for 60 min) and after blood restoration (120 min observation) included systemic blood pressure, heart rate, arteriolar and venular diameter, sensitivity to epinephrine, velocity and volumetric flow rate. These findings were correlated with 24-hr survival statistics. The response to hemorrhagic hypotension is a reflection of two separate adjustments, cardiac output and peripheral vascular behavior. In survivors, the microvascular sequelae following blood replacement was one of continuous improvement of muscle perfusion, whereas in nonsurvivors the picture was one of progressive deterioration. The consistent hallmark of irreversibility, arteriolar hyposensitivity, was associated with a continuous falling off in mean arterial pressure despite restoration of normal blood volume.

Abdominal Muscles↗
PubMed1985

The microvasculature in skeletal muscle. III. Venous network anatomy in normotensive and spontaneously hypertensive rats.

A quantitative description of the anatomical arrangement of venules in the spinotrapezius muscle of mature (12-15 week old) Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) is provided. In both strains, asymmetric, dichotomous collecting venule trees route blood from the capillaries to a network of interconnected or arcade venules which spans the entire muscle. The arcade network is drained of blood through several draining venules which exit the muscle. A new branching scheme is proposed for the venular microvascular network. Comparison of WKY and SHR values shows that the arcade venules in the WKY are, on the average, narrower. Conversely, SHR postcapillary vessels are narrower than those in the WKY. Aside from these differences, however, the venular microvasculature and network pattern in the two strains is similar.

Animals↗